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Two-component Turing reaction-diffusion models can explain how mother centrioles break PLK4 symmetry to generate a single daughter

Wilmott, Z. W.; Goriely, A.; Raff, J. W.

2023-02-03 cell biology
10.1101/2023.02.02.526828 bioRxiv
Show abstract

Centrioles duplicate when a mother centriole gives birth to a daughter that grows from its side. Polo-like-kinase 4 (PLK4), the master regulator of centriole duplication, is recruited symmetrically around the mother centriole, but it then concentrates at a single focus that defines the daughter centriole assembly site. How PLK4 breaks symmetry is unclear. Here, we propose that phosphorylated and unphosphorylated species of PLK4 form the two components of a classical Turing reaction-diffusion system. These two components bind-to/unbind-from the surface of the mother centriole at different rates, allowing a slow-diffusing activator species of PLK4 to accumulate at a single site on the mother, while a fast-diffusing inhibitor species of PLK4 suppresses activator accumulation around the rest of the centriole. This "short-range activation/long-range inhibition", inherent to Turing-systems, can drive PLK4 symmetry breaking on a continuous centriole surface, with PLK4 overexpression producing multiple PLK4 foci and PLK4 kinase inhibition leading to uniform PLK4 accumulation--as observed experimentally.

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